Infectious Agent and Immune Response Characteristics of Chronic Enterocolitis in Captive Rhesus Macaques

Abstract

Chronic enterocolitis is the leading cause of morbidity in colonies of captive rhesus macaques (Macaca mulatta). This study's aim was to identify the common enteric pathogens frequently associated with chronic enterocolitis in normal, immunocompetent rhesus monkeys and to elucidate the influence of this clinical syndrome on the host immune system. We analyzed the fecal specimens from 100 rhesus macaques with or without clinical symptoms of chronic diarrhea. Retrospective analysis revealed an increased incidence of Campylobacter spp. (Campylobacter coli and Campylobacter jejuni), Shigella flexneri, Yersinia enterocolitica, adenovirus, and Strongyloides fulleborni in samples collected from animals with chronic diarrhea (P < 0.05). The presence of additional enteric pathogens, such as Escherichia coli, carrying the eaeA intimin or Stx2c Shiga toxin virulence genes, Balantidium coli, Giardia lamblia, Enterocytozoon bieneusi, and Trichuris trichiura was found in all animals regardless of whether diarrhea was present. In addition, the upregulation of interleukin-1␣ (IL-1␣), IL-3, and tumor necrosis factor alpha cytokine genes, accompanied by an increased presence of activated (CD4 ؉ CD69 ؉ ) T lymphocytes was found in gut-associated lymphoid tissues collected from animals with chronic enterocolitis and diarrhea in comparison with clinically healthy controls (P < 0.05). These data indicate that chronic enterocolitis and diarrhea are associated, in part, with a variety of enteric pathogens and highlight the importance of defining the microbiological status of nonhuman primates used for infectious disease studies. The data also suggest that chronic colitis in rhesus macaques may have potential as a model of inflammatory bowel disease in humans.

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

“…These 10 animals were clinically monitored on a daily basis, and stool specimens were collected each day and examined for the presence of rotavirus antigen. Blood specimens were also collected on a monthly basis and examined for evidence of seroconversion to rotavirus, i.e., a Ն4-fold increase in the level of serum rotavirus IgA or IgG (35,42). Two months following detection of rotavirus and subsequent seroconversion, mononuclear cells were isolated from the peripheral blood of three animals (EA17, ED29, and EA42) and evaluated for the presence of rotavirus-specific T cells.…”

Naturally occurring infections in non-human primates (NHP) and immunotoxicity implications: Discussion sessions

“…First and foremost, animal welfare should be the primary concern, and a qualified veterinarian should thoroughly examine the animals and provide guidance on their care. Gastrointestinal disturbances are quite common in outbred monkey colonies and can lead to rapid debilitation and mortality in rhesus macaques (Hird et al, 1984;George and Lerche, 1990;Elmore et al, 1992;Sestak et al, 2003). This is complicated by the low reserve capacity of body weight in several monkey species, particularly the more commonly-used cynomolgus macaques, which may be only 2-5 kg in weight.…”

Establishment of a non-human primate Campylobacter disease model for the pre-clinical evaluation of Campylobacter vaccine formulations

“…In colonies of captive M. mulatta, recurring diarrhea (chronic enterocolitis) is the leading cause of animal morbidity [24][25][26]. Chronic enterocolitis and diarrhea are associated with a variety of enteric pathogens including C. coli, C. jejuni, Shigella flexneri, Yersinia enterocolitica, adenovirus, and Strongyloides fulleborni [27].…”